POS0774 ANTI-Sm AUTOANTIBODIES IDENTIFY A PHENOTYPE OF SEVERE SLE WITH AN ASSOCIATED SERUM BIOMARKER PROFILE
Authors: A. Hoi, S. Toor, J. Monk, J. Chang, R. Koelmeyer, A. Papadaki, J. Peters, F. Vincent, J. Ooi, E. F. Morand
Journal: Annals of the Rheumatic Diseases (2022)

Background Antibodies to Smith (Sm) have been described as one of the most specific autoantibodies for systemic lupus erythematosus (SLE). Other than its association with lupus nephritis, there is, however, limited understanding of its clinical significance 1,2 . Objectives To describe clinical associations and serum protein profiles of anti-Sm positivity in SLE. Methods Patients fulfilling SLE classification criteria who were followed longitudinally in a prospective multicentre cohort were studied according to their baseline anti-Sm antibody status. Comparison between Sm+ and Sm- patients was made using descriptive statistics. Clinical associations of Sm positivity with patient disease characteristics were studied using logistic regression. In a subset, 211 serum analytes were measured using Quantibody, Luminex and ELISA assays. Associations between serum proteins and Sm positivity were studied using Least Absolute Shrinkage and Selection Operator (LASSO) penalised regression, adjusting for demographics (age, sex, ethnicity) and medication use Results 383 patients were studied with median (IQR) follow-up of 4.9 (2,9) years; 65 (17%) had positive anti-Sm antibodies. Sm+ patients were significantly more likely to be of non-European ancestry (OR 2.73, 95% CI 1.55-4.82, p&lt;0.001), and to be positive for anti-dsDNA antibodies (OR 2.8, 95% CI 2.3-3.4, p&lt;0.001), anti-RNP antibodies (OR 15.7, 95% CI 13.9-17.8, p&lt;0.001), direct anti-globulin test (OR 2.36, 95% CI 2.07-2.7, p&lt;0.001) and hypocomplementemia (OR 7.73, 95% CI 5.1-11.7, p&lt;0.001). Sm+ patients were significantly more likely to have active disease during the observation period in a range of organ domains, including mucocutaneous, renal, vasculitis and fever. More Sm+ patients had episodes of High Disease Activity Status (HDAS, SLEDAI-2K ≧10) 3 (OR 3.07, 95% CI 1.70-5.54, p&lt;0.001) and persistent active disease (time-adjusted mean SLEDAI-2K &gt; 4) (OR 3.23. 95% CI 1.84-5.70, p&lt;0.001). Conversely, fewer Sm+ patients attained LLDAS for ≥50% observed time (19.7% vs 41.8%, p=0.002). Sm+ patients were more likely to be treated with glucocorticoids, immunosuppressants, and rituximab. There was no significant difference in damage accrual between Sm + and Sm - patients. In serum protein analysis (n=197, 29 Sm+), LASSO modelling retained 3 proteins associated with Sm+ status, CXCL13, IL1RL1 and FLT1, along with Asian ethnicity and age. In analysis including pairwise interaction between predictors, 28 Sm+ associated proteins were identified, including CCL4, VCAM1, IL1RL1, Fcg R IIB/C, TDGF1, CEACAM1, TIMP1, BMP5, GDF15, and TNFRSF17. Conclusion Anti-Sm autoantibodies, present in 17% of SLE patients, were strongly associated with classical disease manifestations, more severe disease activity, and a specific serological and proteomic profile. These findings suggest anti-Sm+ SLE as a specific disease subset. References [1]Barada, FA., B.S. Andrews, J.S. Davis, R.P. Taylor, Antibodies to Sm in patients with systemic lupus erythematosus. Correlation of Sm antibody titers with disease activity and other laboratory parameters. Arthritis Rheum, 1981. 24 :1236-1244 [2]Arroyo-Avilla, M, Y. Santiago-Casas, G.McGwin, R.S. Cantor, M. Petri, R. Ramsey-Goldman, J.D. Reveille, R.P.Kimberly, G.S. Alarcon, L.M.Vila, E.E. Brown. Clinical Associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort. 2015. 34 :1217-1223 [3]Koelmeyer, R., H.T. Nim, M. Nikpour, Y.B. Sun, A. Kao, O. Guenther, E. Morand, and A. Hoi, High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus. Lupus Sci Med, 2020. 7 (1). Acknowledgements I would like to acknowledge participants and clinicians involved with the Australian Lupus Registry &amp; Biobank Disclosure of Interests None declared